The goal of this project is to characterize the function of B lymphocyte membrane molecules. Previous findings indicated that the FcGamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens, c) Lym antigens, d) surface IgM, and e) surface IgD. Each of these interactions is distinct, specific, and non-random. Studies with a B lmyphocyte hybridoma (2.4G2) have shown that this hybridoma produces a low molecular weight substance(s) which triggers B lymphocytes to both proliferative and secrete antibody. This result suggests that certain B lymphocytes may produce factor(s) with helper activity. Studies utilizing antigen-antibody complexes and monoclonal anti-Fcy receptor antibodies indicate that B lymphocyt FcGamma receptors cross-liniked by their physiologic ligand down-regulate B lymphocyte differentiation without affecting proliferation. Resting but not activated B lymphocytes are susceptible to this negative regulation. Occupancy of B lymphocyte surface IgM by a separate ligand is necessary for inhibition to occur, suggesting that the previously described interaction between these two membrane receptors is involved in generating the negative signal. Monoclonal anti-Fcy receptor antibodies on a Sepharose matrix but not in soluble form effect B lymphocyte function in a fashion similar to antigen antibody complexes. This result suggests that certain monoclonal antibodies specific for cell surface receptors must be presented in a form which will produce effective cross-linking in order to obtain functional effects. Covalently cross-linked monoclonal antibodies are being prepared to test this hypothesis. Recently, several monoclonal antibodies have been produced which react primarily with activated B lymphocytes. The molecules recognized by these antibodies will be characterized chemically and functionally. These molecules may be receptors for growth or differentiation factors.